Several animal tumor models have been established to evaluate the in vivo efficacy of monoclonal antibodies: a) a model for metastatic human melanoma has been developed in nude mice with brachial and axillary lymph node metastases, but no gross viscereal metastases, produced by s.c. or i.v. inoculation of 500,000 cells of the melanoma cell line, FeMX Met II. b) Strain 2 guinea pigs bearing the syngeneic line 10 hepatocarcinoma were treated with immunoconjugates of the D3 monoclonal antibody with the A chain of abrin or diphtheria toxins. The maximum tolerated doses for the diphtheria and abrin conjugates were 25 and 85 Mug's, respectively, with toxicity consisting of severe loss of body weight, ruffled coats, and lethargy. Some retardation of tumor growth was seen after administration of 100 Mug of abrin conjugate to animals with tumors greater than 1 cm in diameter. c) To select drugs for immunoconjugate studies, a variety of chemotherapeutic agents were evaluated for in vivo efficacy against a transplantable spontaneous mammary carcinoma in guinea pigs. Cyclophosphamide was found to be most effective against established tumors, with less effect seen with Alkeran and cis-platinum, and no effect observed with adriamycin or 5-fluorouracil.